000266883 001__ 266883
000266883 005__ 20190627122413.0
000266883 022__ $$a0898-6568
000266883 022__ $$a1873-3913
000266883 0247_ $$a10.1016/j.cellsig.2019.03.012$$2doi
000266883 02470 $$2isi$$a000468251000006
000266883 037__ $$aARTICLE
000266883 245__ $$aIdentification of novel PCTAIRE-1/CDK16 substrates using a chemical genetic screen
000266883 260__ $$c2019-07-01
000266883 269__ $$a2019-07-01
000266883 336__ $$aJournal Articles
000266883 520__ $$aPCTAIRE-1 (also known as cyclin-dependent protein kinase (CDK) 16), is a Ser/Thr kinase that has been implicated in many cellular processes, including cell cycle, spermatogenesis, neurite outgrowth, and vesicle trafficking. Most recently, it has been proposed as a novel X-linked intellectual disability (XLID) gene, where loss-of-function mutations have been identified in human patients. The precise molecular mechanisms that regulate PCTAIRE-1 remained largely obscure, and only a few cellular targets/substrates have been proposed with no clear functional significance. We and others recently showed that cyclin Y binds and activates PCTAIRE-1 via phosphorylation and 14-3-3 binding. In order to understand the physiological role that PCTAIRE-1 plays in brain, we have performed a chemical genetic screen in vitro using an engineered PCTAIRE-1/cyclin Y complex and mouse brain extracts. Our screen has identified potential PCTAIRE-1 substrates (AP2-Associated Kinase 1 (AAK1), dynamin 1, and synaptojanin 1) in brain that have been shown to regulate crucial steps of receptor endocytosis, and are involved in control of neuronal synaptic transmission. Furthermore, mass spectrometry and protein sequence analyses have identified potential PCTAIRE-1 regulated phosphorylation sites on AAK1 and we validated their PCTAIRE-1 dependence in a cellular study and/or brain tissue lysates. Our results shed light onto the missing link between PCTAIRE-1 regulation and proposed physiological functions, and provide a basis upon which to further study PCTAIRE-1 function in vivo and its potential role in neuronal/brain disorders.
000266883 542__ $$fCC BY-NC-ND
000266883 650__ $$aCell Biology
000266883 650__ $$aCell Biology
000266883 6531_ $$apctaire-1
000266883 6531_ $$apctk1
000266883 6531_ $$accny
000266883 6531_ $$acyclin
000266883 6531_ $$aap2-associated kinase 1
000266883 6531_ $$aaak1
000266883 6531_ $$adynamin 1
000266883 6531_ $$asynaptojanin 1
000266883 6531_ $$ax-linked intellectual disability
000266883 6531_ $$axlid
000266883 6531_ $$achemical genetics
000266883 6531_ $$acyclin y
000266883 6531_ $$aneuronal migration
000266883 6531_ $$agatekeeper residue
000266883 6531_ $$aregulatory subunit
000266883 6531_ $$aneurite outgrowth
000266883 6531_ $$aprotein-kinases
000266883 6531_ $$amouse-brain
000266883 6531_ $$asynaptojanin
000266883 6531_ $$aphosphorylation
000266883 6531_ $$aspecificity
000266883 700__ $$aShehata, Saifeldin N.
000266883 700__ $$aDeak, Maria
000266883 700__ $$g254149$$aCollodet, Caterina
000266883 700__ $$aSpiegl, S. F.
000266883 700__ $$aGeley, Stephan
000266883 700__ $$aSumpton, David
000266883 700__ $$aSakamoto, Kei
000266883 773__ $$q53-61$$j59$$tCellular Signalling
000266883 8564_ $$uhttps://infoscience.epfl.ch/record/266883/files/Identification%20of%20novel%20PCTAIRE-1%20CDK16%20substrates%20using%20a%20chemical%20genetic%20screen.pdf$$zFinal$$s1139553
000266883 8560_ $$fbeatrice.marselli@epfl.ch
000266883 909C0 $$xU10445$$pSV$$0252372
000266883 909CO $$ooai:infoscience.epfl.ch:266883$$particle$$pSV
000266883 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000266883 981__ $$aoverwrite
000266883 980__ $$aARTICLE